We have demonstrated that GABA in rat pineal glands, presumed to localized in glial cells, can be modified by altering the neuronal be activity in these glands. GABA content of these glands was 2x10 to the minus 5th power M,and these levels could be elevated significantly by inhibition of GABA-transaminase with amino-oxy acetic acid. We determined the activity of GAD, the synthesizing enzyme for GABA, and found it to be 176 picomoles GABA formed/mg protein-min. Thus, we demonstrated that GABA machinery exists in the pineal gland. We further showed that GABA can elevate levels of endogenous cycle GMP but not that of cyclic AMP, in the presence of low concentrations of norepinephrine without altering basal levels of these nucleotides. Since cyclic GMP is presynaptic this suggest that GABA may play a role in the regulation of norepinephrine release in rat pineal glands. In addition, We were able to obtain evidence for the existence of GABA binding sites in the rat and bovine pineal glands. Now that some indication exists for the regulation and functional significance of GABA in this system, we will carry out experiments to characterize the type of adrenergic receptors that may exist on the glial cells in this gland. We will construct a complete model for the regulation of glial GABA and the modification of synaptic transmission by this inhibitory transmitter and then we will examine the effects of various anxiolytics (such as benzodiazepines) on this model system. This will permit us to arrive at the mechanism by which anxiolytics exert their therapeutic effects on complex neuronal pathways.